The Cancer Epidemiology and Chemoprevention Research Program engages a multidisciplinary group of laboratory investigators, population scientists, and clinicians who work collaboratively to elucidate the etiology of cancer and to develop Chemoprevention strategies. Emphasis is placed on mechanistic approaches as the basis for translating work from the bench to the bedside and to the community. The Program fosters discovery of novel chemopreventive agents by identifying their critical biologic targets and ultimately testing their efficacy on markers of early biologic response and on clinical disease. The Program further promotes investigations to identify carcinogenic factors and their biological effects at the molecular, genetic, and protein levels as well as inquiries into the environmental and biologic factors that modify these effects in populations. These efforts collectively involve observational studies, clinical trials (including proofof- principle and definitive Phase III trials), biomarker development, in vitro investigations, and animal studies including the use of genetically modified mice. Recent programmatic highlights include: (1) identifying induced cyclin proteolysis as a novel chemopreventive target;(2) successful conduct of proof-of-principle trials to validate this target in the clinic;(3) completion of large-scale, placebo-controlled randomized Chemoprevention trials, with findings of a reduced risk of colorectal adenoma following low-dose aspirin supplementation;and (4) extension of population-based molecular epidemiologic studies leading to detection of an association between human papillomavirus infection and squamous cell carcinoma of the skin in the general population. By promoting collaborations among basic and clinical scientists from 7 departments, the 19-member program has created advances that no single investigator could have made. Program members conduct research projects with current annual total cost funding of $10.9 million ($7.9 million from NCI, 72%). Program members published more than 300 papers during the renewal period, of which 32% derived from intra-programmatic and 33% from inter-programmatic collaborations. Over the next five years, we will continue to support initiatives with the greatest potential for clinical and public health impact on reducing the cancer burden, and to build on our growing areas of excellence in Chemoprevention, population-based studies of cancer incidence and progression, and the effects of early life exposures. The Program aims at continuing to strengthen its scientific accomplishments by organizing and fostering formal and informal mechanisms that promote collaboration and interactive projects between epidemiologists, laboratory scientists, and clinicians.